Abstract 11091: Failure of Right Ventricular Adaptation to Pressure Overload Due to a Profound Deficiency in Adenylate Kinase 1 and Impaired Ventricular Energetics
| Autor: | Jason Zelt, Virgilio Cadete, Yupu Deng, Rafael Godoy, Alexanne Cuillerier, Katelynn Rowe, Mohammad Abdul-Ghani, Lynn Megeney, Yan Burelle, Antonio Giulivi, Alexandre F STEWART, Steeve Provencher, Sandra Breuils-bonnet, sébastien bonnet, Robert deKemp, Rob S Beanlands, Lisa Mielniczuk, Duncan J Stewart |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Circulation. 144 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circ.144.suppl_1.11091 |
| Popis: | Introduction: Interindividual heterogeneity in the ability of the right ventricular (RV) to adapt to pressure overload in pulmonary hypertension (PH) is likely influenced by genetic determinants. We took advantage of strain-dependent, maladaptive RV remodeling in Fischer compared to Sprague-Dawley (SD) rats to define the molecular and genetic mechanisms that predispose to development of RV failure in PH. Methods/Results: In the SU5416/hypoxia(SUHx) PH model, Fischer rats exhibited RV failure and 100% mortality by 5-weeks, whereas SD rats showed preserved RV function and 88% survival beyond 9 weeks (pIn vivo oxidative metabolism, assessed by [ 11 C]acetate PET, was increased in Fischer rats at 4 weeks (p2 , respectively; p10-fold reduction, P Conclusion: Fischer rats with AK1 deficiency have inefficient energetics likely related to reduced ATP shuttling from the mitochondria to the contractile fibers, which represents a novel mechanism for RV failure in response to chronic increases in afterload. |
| Databáze: | OpenAIRE |
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